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Good Clinical Practice
(GCP)
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What is GCP?
Good Clinical Practice (GCP) is defined as a
standard for the design, conduct, performance,
monitoring, auditing, recording, analyses andreporting of clinical trials that provides
assurance that the data and reported results
are credible and accurate, and that the rights,
integrity and confidentiality of trial subjects are
protected
(ICH GCP)
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GCP principles summary (1)
Rights, safety & well being of subjects prevailover interests of science and society
Individuals involved in trial should be qualifiedby education, training and experience toperform his/her tasks
Trials shall be scientifically sound and guided
by ethical principles in all their aspects Necessary procedures to secure the quality of
every aspect of the trial shall be compliedwith
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GCP principles summary (2)
Available non-clinical and clinical information on an
IMP shall be adequate to support the trial
Conducted according to Helsinki Declaration (1996)
Protocol shall provide inclusion and exclusion criteria,monitoring and publication policy
Investigator/sponsor shall consider all relevant
guidance
Information recorded, handled and stored to allowaccurate reporting, interpretation and verification and
confidentiality of subjects records
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GCP compliance
ICH GCP section 5.18.3 allows individual
researchers to assess the needs of their trial
and apply GCP appropriately central monitoring in conjunction with
procedures such as investigators training
and meetings and extensive written guidance
can assure appropriate conduct of the trial inaccordance with GCP.
On-site monitoring not compulsory
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Who must comply with GCP?
All individuals involved in any aspect of
the trial must be suitably qualified to be
able to comply with GCP. Sponsors/CIs are responsible for
ensuring that all staff are able to comply
with GCP.
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What counts as qualified?
According to GCP each individual involved in
conducting a trial shall be qualified by
education, training, and experience to performhis or her respective task(s)(GCP principle 8)
Education
Training
Experience
There is no GCP qualification
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Education
Individuals must be educated to be able
to competently perform their specific trial
task.
Clinicians must be clinically qualified
Statisticians must be qualified
Managers must be appropriately educated
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Training
There are a variety of courses and seminars
currently available
Employer induction courses Industry courses
E-learning (Institute of Clinical Research)
Private courses (usually run by freelance
consultant) Host institution courses
Trial specific workshops
Investigators meetings
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Experience
On-the-job learning
Discovering what is required
Doing the job (sometimes wrongly)
Cascading information and knowledge
through teams/units
Talking to other trialists
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Rationale and documentation
As there is no formal qualification it is
essential to keep up to date records of
training.
Describe the rationale for the methods of
GCP training used in the trial
Document courses/seminars/meetingsattended by staff on a training file
Keep it up to date
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Approvals and permissions
Ethics committee approval
Clinical Trials Authorisation (IMPs)
R & D permission
Sponsor approval
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Trial Master File
Essential documents are defined as documents whichindividually and collectively permit evaluation of the conduct of atrial and the quality of the data produced and should be retainedin the Trial Master File
Documents to be contained in the Master File will varyaccording to the trial
Trial Master File should be held at the principal site by the ChiefInvestigator or at the Co-ordinating Centre
Investigators Site Files are held by the Principle Investigators atsites and contains copies of the essential documents, localapprovals, signed consent forms and completed data forms.
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Standard Operating Procedures
There should be a written description of all trial management
systems and conventions. This documentation forms the
operating procedures, often referred to as Standard Operating
Procedures (SOPs).
SOPS are usually generic to the Trials Unit or
Institution.
A trial specific operating procedure must be developed
for each trial. These may be called MOPs (Modified Operating
Procedures) or TSOPs (Trial Specific Operating Procedures).
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Trial monitoring
ICH-GCP Extent and Nature of Monitoring
The sponsor should ensure that the trials are adequately monitored. The
sponsor should determine the appropriate extent and nature of monitoring.
The determination of the extent and nature of monitoring should be based
on considerations such as the objective, purpose, design, complexity,
blinding, size,and endpoints of the trial. In general there is a need for on-
site monitoring, before, during, and after the trial; however, in exceptional
circumstances the sponsor may determine that central monitoring in
conjunction with procedures such as investigators training and meetings,
and extensive written guidance can assure appropriate conduct of the trialin accordance with GCP. Statistically controlled sampling may be an
acceptable method for selecting the data to be verified.
5.18.3
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Informed consent
Informed consent personal autonomy
a competent individual should have the right
to determine those discretionary risks he/sheis willing to accept for whatever benefitshe/she perceives may result .
Weil WB. Informing and Consenting
In Silverman W. Wheres the evidence? OUP 1997
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Informed consent
Following the second world war and the Nurembergtrials, the Nuremberg Code and Declaration of Helsinkiwas agreed worldwide as a charter to protectpeople/patients against human experimentation
Up until 1995 USA, Japan and Europe worked todifferent standards in the conduct of clinical trials
1995 ICH-GCP was implemented a global standard
2001 EU Directive set out regulations for clinical trialsof medicines conducted within the EU
2004 (May) the UK implemented the Directive and theUK Regulations became law
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Consent
Ethics committee must approve all information given tothe trial participant
Statements to comply with Data Protection Act mustalso be included in the PIL
Consent forms and patient information leaflets musttake into account recent legislation
SOPs required describing who is authorised toconduct consent procedure
Centre personnel who participate in the consentprocedure should be listed on the delegation log,provide CVs and be trained!!
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Consent
Decision time: confusing
ICH states ample time to decide The Directive does not state any time-frame
6-day rule in Ireland (being revised in 2006)
UK has no time -frame
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Consent procedures
Given freely
Face to face
Telephone Watch
Listen
Learn What works well?
Share
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Safety reporting
Adverse events (annual)
Serious Adverse Events (SAEs)
(within 7 days)
Serious Adverse Reactions (SARs)
(within 7 days)
Suspected Unexpected Serious Adverse
Reactions (SUSARs)
(expedited)
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Expedited reporting
Fatal or life threatening SUSARS:
not later than 7 days after the person responsible for
pharmacovigilance received information that the case
fulfilled the criteria for a fatal or life threateningSUSAR, and any follow up information within a further
8 days.
All other SUSARs:
not later than 15 days after the sponsor forpharmacovigilance had information that the case
fulfilled the criteria for a SUSAR.
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Archiving
Essential documents NOT used in a
regulatory submission must be retained for
at least FIVE years after the end of the trial Destruction of essential documents and a
record of the destruction must also be
retained for a furtherFIVE years
Local R&D offices may also impose a
retention period
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Good Clinical Practice in Practice
Be pragmatic in your approach to GCP
Use your Rick Assessment to justify your
approach Document the rationale behind the decisions
Be brave